Impact of PCSK9 Inhibitor Funding Decisions on Cardiovascular Outcomes

Impact of Funding Decisions on Cardiovascular Outcomes with Alternative Lipid-Lowering Therapies

Introduction to Lipid-Lowering Treatments

For over two decades, statins have served as the primary treatment for hyperlipidemia, playing a crucial role in preventing atherosclerotic cardiovascular disease (ASCVD). However, as medical science advances, it is essential to explore future treatment options for hyperlipidemia.

Understanding PCSK9 Inhibitors

Biopharmaceuticals are emerging as promising alternatives, particularly proprotein convertase subtilisin/kexin type 9 inhibitors, commonly referred to as PCSK9 inhibitors or PCSK9i. This class of drugs aims to revolutionize the management of lipid levels.

Mechanism of Action

LDL cholesterol (LDL-C) receptors, located on cell surfaces, facilitate the transport of circulating LDL-C into cells, notably the liver, thus reducing LDL-C levels in the bloodstream. PCSK9 is a protein that binds to these LDL receptors, impairing their ability to transport LDL cholesterol into cells. By inhibiting PCSK9, the availability of LDL receptors increases, promoting the removal of LDL-C from the blood.

Aims of the Study

The effectiveness of PCSK9 inhibitors in lowering LDL-C and reducing cardiovascular disease risk has been validated in several studies. Currently, two PCSK9 inhibitors, Praluent (Alirocumab) and Repatha (Evolocumab), are available, both being monoclonal antibodies with high costs. Initially priced at around $14,000 annually upon their 2015 launch, the current costs range between $5,000 and $10,000 annually. Given this expense, the decisions made by payers regarding the funding of PCSK9 inhibitors could significantly influence their impact on cardiovascular health.

A recent study published in *Circulation: Cardiovascular Quality and Outcomes* investigates how payer decisions to fund PCSK9 inhibitors affect cardiovascular outcomes, rather than focusing solely on the drug’s effectiveness.

Study Methodology

This study employed a propensity score matched, retrospective cohort design using a vast healthcare claims dataset comprising 221 million patients. A limitation of retrospective studies is the lack of control over patient grouping, necessitating the use of statistical techniques like propensity score matching to ensure fair comparisons.

Study Results

The findings revealed that patients whose prescriptions for PCSK9 inhibitors were denied or abandoned experienced a higher incidence of cardiovascular events compared to those whose prescriptions were funded. Specifically, rejected prescriptions correlated with a 10% increased risk of cardiac events (hazard ratio 1.10), while abandoned prescriptions led to a 12% increased risk (hazard ratio 1.12).

Although hazard ratios provide insight into relative risk, they do not indicate event frequency. The incidence density rate (IDR) data included in the study indicated an additional 0.59 events per 100 person-years in the rejected group and an extra 0.5 events per 100 person-years in the abandoned group compared to the funded prescriptions.

The study also analyzed hazard ratios across various patient subgroups, focusing on familial hypercholesterolemia (FH) and clinical ASCVD. Patients presenting both FH and ASCVD faced over five times greater risk of cardiovascular events than those without these risk factors.

Implications for Clinical Practice

The implications for clinical practice are significant. Two well-established factors remain: PCSK9 inhibitors are effective, yet they are costly. This study introduces additional considerations that may influence the prescription of PCSK9 inhibitors. Notably, patients with both FH and ASCVD are at increased cardiovascular risk, yet a prior analysis indicated that 63% of PCSK9i prescriptions for this subgroup were rejected by payers.

The high abandonment rates underscore that payer approval alone does not guarantee patient access to prescribed treatments. High co-payment costs and the subcutaneous route of administration, which some patients find undesirable, contribute to these abandonment rates.

To justify funding for high-cost treatments like PCSK9 inhibitors, they must demonstrate cost-effectiveness. The findings suggest that certain high-risk subgroups may justify the cost of PCSK9 inhibitors, as previous analyses in Europe have shown these treatments to be cost-effective in similar populations. Moreover, future prescriptions may need to consider factors affecting patient adherence, such as the feasibility of covering co-payments.

Conclusion

The study emphasizes the importance of payer decisions in the accessibility of PCSK9 inhibitors and their subsequent impact on cardiovascular outcomes. As healthcare continues to evolve, ongoing evaluation of treatment efficacy and cost-effectiveness will be crucial in optimizing patient care.

References

1. Myers KD, Farboodi N, Mwamburi M, Howard W, Staszak D, Gidding S, et al. Effect of Access to Prescribed PCSK9 Inhibitors on Cardiovascular Outcomes. Circulation Cardiovascular quality and outcomes. 2019;12(8):e005404.
2. Knowles JW, Howard WB, Karayan L, Baum SJ, Wilemon KA, Ballantyne CM, et al. Access to Nonstatin Lipid-Lowering Therapies in Patients at High Risk of Atherosclerotic Cardiovascular Disease. Circulation. 2017;135(22):2204-6.
3. Korman M, Wisloff T. Modelling the cost-effectiveness of PCSK9 inhibitors vs. ezetimibe through LDL-C reductions in a Norwegian setting. European heart journal Cardiovascular pharmacotherapy. 2018;4(1):15-22.